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New in the non-rheumatology journals, much about pain: A review based on 2012 fibromyalgia guidelines from Canada, a viewpoint on safe use of opioids, the evidence to back spinal pain interventions. Also: fast-track arthroplasty, and more newfound genes.
Last week's articles on rheumatology topics in the major nonspecialty journals
CMAJ, online first, May 6, 2013. Free full text.
Fibromyalgia is a not an inflammatory soft-tissue disorder. It is a neuropathic process involving abnormalities of pain processing at various levels of the nervous system, says this review based on 2012 guidelines, adding that primary care physicians, not rheumatologists, are the most appropriate providers for this condition. Treatments should dampen ascending pain signals and augment descending mechanisms of pain inhibition, it adds. Although evidence for complementary and alternative medicine is insufficient, and because the effects of individual treatments may be modest, the guidelines recommend a wide and multimodal range of therapies, from anti-inflammatory agents, anti-convulsants, and opioids to physical interventions such as massage, heat and cold, transcutaneous electrical nerve stimulation, and acupuncture. The review confronts the issues around defining fibromyalgia as a disability, noting that patients in the workforce have less severe symptoms and a better quality of life than those who are unemployed.
Viewpoint: Opioid Analgesics-Risky Drugs, Not Risky PatientsJAMA, published online May 9, 2013. Free full text.
Despite the claims of industry-sponsored programs, says this editorial, no screening tool can reliably identify patients who are at high risk of abuse or death from opioids: “The most important risk factor for opioid analgesic-associated dependence or overdose is not a feature of any individual patient but instead simply involves receiving a prescription for opioids.” Low-risk patients given high doses are at high risk of overdose. Patients should be prescribed opioids according to the risk/benefit ratio of opioids for that patient’s current situation, not the patient’s substance use history. For chronic noncancer pain, systematic reviews have not found sufficient evidence that long-term opioid use is more effective than other treatments. . For pain control at the end of life, however, the benefits often outweigh the risks.
An Update of Comprehensive Evidence-Based Guidelines for Interventional Techniques in Chronic Spinal PainPain Physician, April 2013. Free full text.
The evidence is judged fair to good for 62% of diagnostic and 52% of therapeutic interventions assessed in this review, covering lumbar spine, cervical spine, thoracic spine, implantables, and anticoagulation.
Hip and Knee Arthroplasty
Fast-track hip and knee arthroplastyLancet, May 11, 2013. Full text $31.50
An interesting review of “fast-track” arthroplasty in European medical systems, implemented to enhance recovery and reduce morbidity with cost reductions as a secondary benefit. Current hospital stays after total hip and knee arthroplasty in Europe are often between 6-11 days, but they have been reduced to 5 days in large-scale fast-track programs, although a reported 2-4 days may be with discharge to rehabilitation. Critical areas for implementation are effective postoperative pain management, a better understanding of the pathogenesis of muscle weakness, management of preoperative anemia, the proper period for thromboprophylaxis, and postoperative delirium and cognitive dysfunction. Postoperative stays of 1-2 days with discharge to home are possible.
Retinal Vasculitis, Aneurysms, and Neovascularization in Blau SyndromeJAMA Ophthalmol, May 2013. Full text $30
A 6-year-old boy with 20/800 OD and 20/20 OS had indistinct disc margins, neovascularization, vascular sheathing, and obliteration of peripheral vessels on the right eye. The left fundus had neovascularization and arteriolar aneurysms. Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) was considered, but first, inflammatory disease had to be ruled out. Elevated angiotensin-converting enzyme (ACE) levels prompted genetic testing, which found two mutations on a gene associated with Blau syndrome and Crohn disease. The inflammatory symptoms fit a diagnosis of Blau syndrome, and the patient was treated with peripheral laser coagulation. Blau syndrome is rare, with only 136 cases reported, but is potentially life-threatening.
WNT1 Mutations in Early-Onset Osteoporosis and Osteogenesis ImperfectaN Engl J Med, May 9, 2013. Full text $15
Most osteogenesis imperfecta (OI) is caused by mutations in collagen. Two families had severe, early-onset osteogenesis imperfecta because of a mutation in the WNT1 gene instead. WNT signaling is known to regulate osteoblasts, osteoclasts and osteocytes. This study clarifies that mechanism. WNT1 is expressed in the hematopoietic stem-cell niche of the bone marrow, and this study supports a role for hematopoietic cells in regulating bone formation, with WNT1 a key signaling marker.
Mutations in B3GALT6, which Encodes a Glycosaminoglycan Linker Region Enzyme, Cause a Spectrum of Skeletal and Connective Tissue DisordersAmerican Journal of Human Genetics, May 9, 2013. Free full text.
After screening seven families, loss-of-function mutations in B3GALT6 were identified as the cause of spondyloepimetaphyseal dysplasia (SEMD) with joint laxity type 1 (SEMD-JL1). Recessive loss-of-function mutations in the enzyme B3GALT6 result in a range of skeletal and connective tissue disorders characterized by lax skin, muscle hypotonia, joint dislocation and spinal deformity, which were previously thought to belong to different families of diseases. B3GALT6 is required to synthesize the glycosaminoglycan side chains of proteoglycans, which are structural and regulatory components of the extracellular matrix. In a subsequent study, B3GALT6 was also found responsible for Ehlers-Danlos syndrome (progeroid form). Nonsense mutation in the LGR4 gene is associated with several human diseases and other traitsNature, published online May 5, 2013.Full text $32
Whole-genome screening of Icelandic individuals found a rare nonsense mutation within the LGR4 (leucine-rich-repeat-containing G-protein-coupled receptor 4) gene that is strongly associated with low bone mineral density and osteoporotic fractures. The mutation completely disrupts the function of the receptor and is also associated with electrolyte imbalance, late onset of menarche, reduced testosterone, risk of squamous cell carcinoma of the skin and biliary tract cancer.